Critical events in HIV pathogenesis, including the establishment of persistent viral reservoirs occur shortly after infection. Yet the earliest events following mucosal transmission are not well defined. Understanding these events may provide important information regarding the design of an HIV vaccine. They may also provide new strategies to diminish the size of the viral reservoir. We are testing the hypothesis that HIV gp120 interactions with integrin a4b7 represent an important aspect of HIV transmission and pathogenesis. Integrin a4b7 is not an entry receptor, yet cells expressing this receptor are preferentially infected. The way this occurs is not yet understood. However, the interaction between gp120 and a4b7 holds the potential to impact the design of both vaccines and therapeutic strategies that reduce viral reservoirs. Using an SIV/rhesus macaque model we are investigating the utility of an anti- a4b7 monoclonal antibody in preventing infection. We are also evaluating the utility of this antibody as a therapeutic agent for the treatment of HIV disease.